The understanding of human genetics is rapidly expanding, fueled in part by developments in large-scale sequencing technologies. The results obtained from the sequencing of a genome, however, still present numerous production and bioinformatics challenges. The sheer volume of data obtained in a single sequencing experiment poses a remarkable data analysis challenge. The quality of the data, which often comprise millions to hundreds of millions of small sequence reads, poses yet another challenge. The development of streamlined, highly automated pipelines for data analysis is critical for transition from technology adoption to accelerated research and publication. Many obstacles remain in developing methods, algorithms, and computer program products for the analysis of sequencing data.